The effect of Farnesoid X receptor agonist tropifexor on liver damage in rats with experimental obstructive jaundice

ABSTRACT Purpose: To investigate experimentally the effects of Tropifexor, a farnesoid X receptor agonist, on liver injury in rats with obstructive jaundice. Methods: Forty healthy Wistar albino female rats were divided randomly in selected groups. These groups were the sham group, control group, vehicle solution group, Ursodeoxycholic acid group and Tropifexor group. Experimental obstructive jaundice was created in all groups, except the sham one. In the blood samples obtained, aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), total bilirubin and direct bilirubin levels were established and recorded. Additionally, liver malondialdehyde, myeloperoxidase and catalase enzyme activity in the tissue samples were studied. Histopathological analysis was also performed. Results: No statistical difference was found between the control group and the Tropifexor group when AST, ALT and ALP values were compared. However, it was found that the Tropifexor group had statistically significant decreases in the values of GGT, total bilirubin and direct bilirubin (p < 0.05). Additionally, Tropifexor decreased the median values of malondialdehyde and myeloperoxidase, but this difference was not statistically significant compared to the control group. Finally, the Tropifexor group was statistically significant in recurring histopathological liver damage indicators (p < 0.05). Conclusions: Tropifexor reduced liver damage due to obstructive jaundice.

Pancreatite autoimune / Autoimmune pancreatitis

Pancreatite autoimune é uma entidade caracterizada por processo inflamatório autoimune, no qual há proeminente infiltrado linfocitário associado à fibrose do pâncreas, com disfunção orgânica. Nas últimas quatro décadas, várias descrições morfológicas foram propostas para caracterizar a doença. Recentemente, o termo pancreatite autoimune se tornou largamente aceito, embora, aparentemente, a pancreatite autoimune seja uma doença heterogênea.

Autoimmune pancreatitis is a entity characterized by an autoimmune inflammatory process where there is an outstanding lymphocytic infiltrated associated with fibrosis of pancreas with organic dysfunction. The last four decades, many morphological descriptions have been proposed in order to characterized the disease. Recently, autoimmune pancreatitis term became widely accepted, however, autoimmune pancreatitis is a heterogeneous disease.

Renal ischemia and reperfusion injury: influence of chorpromazine on renal function and lipid peroxidation / Lesão de isquemia e reperfusão renal: influência da clorpromazina na função renal e na peroxidação lipídica

PURPOSE: To evaluate the influence of chlorpromazine (CPZ) on renal function and lipid peroxidation in a rat model of kidney ischemia/reperfusion injury. METHODS: Forty eight Wistar rats underwent a laparotomy for hilar clamping of left kidney with a bulldog clamp for 60 minutes followed by organ reperfusion and contralateral nephrectomy. Of these, 26 received 3mg/kg of CPZ intravenously 15 minutes before renal ischemia (G-E) while the remaining 22 were used as ischemic control group (G-C). Eleven rats of G-E and 8 of G-C were followed for blood urea nitrogen and creatinine determinations before renal ischemia and at 1st, 4th and 7th postoperative days. Samplings of left renal tissue were obtained at 5 minutes (5 rats from each group) and 24 hours (9 G-C and 10 of G-E) of reperfusion for malondialdehy (MDA) content determination. Controls of renal MDA content were determined in kidneys harvested from 6 additional normal rats. RESULTS: Acute renal failure occurred in all animals but levels of BUN and creatinine were significantly lower in G-E (p<0.001). MDA content rose strikingly at 5 minutes of reperfusion in both groups (p>0.05) and returned near to normal levels 24 hours later. CONCLUSION: CPZ conferred partial protection of renal function to kidneys submitted to ischemia/reperfusion injury that seems to be not dependent on inhibition of lipid peroxidation.

OBJETIVO: avaliar a influência da clorpromazina (CPZ) na função renal e na peroxidação lipídica num modelo de lesão de isquemia/reperfusão renal em ratos. MÉTODOS: 48 ratos Wistar foram submetidos à laparotomia para clampamento da artéria renal esquerda durante 60 minutos, seguido da reperfusão e nefrectomia contralateral. Destes animais, 26 receberam 3 mg/kg de CPZ intravenosa 15 minutos antes da isquemia renal (G-E), sendo os 22 animais restantes utilizados como grupo controle isquêmico (G-C). Em 11 ratos do G-E e 8 do G-C foi feita a dosagem de uréia e creatinina sérica antes da isquemia renal e no 1º, 4º e 7º dia pós-operatório. Amostras de tecido do rim esquerdo foram obtidas aos 5 minutos (5 ratos de cada grupo) e 24 horas após reperfusão (9 G-C e 10 G-E) para dosagem de malondialdeído (MDA). Valores controle para níveis de MDA foram obtidos em rins retirados de 6 ratos normais. RESULTADOS: insuficiência renal aguda ocorreu em todos os animais mas os níveis séricos de uréia e creatinina foram significativamente menores no G-E (p<0,001). Os níveis de MDA apresentaram elevação acentuada na avaliação aos 5 minutos de reperfusão em ambos os grupos (p<0,05), retornando a valores próximos aos normais na avaliação com 24 horas. CONCLUSÃO: a CPZ conferiu proteção parcial da função renal aos rins submetidos à lesão de isquemia e reperfusão, aparentemente independente da inibição da peroxidação lipídica.

Ictericia obstructiva asociada a linfoma de Burkitt en un adulto inmunocompetente / Obstructive jaundice associated Burkitt's lymphoma mimicking pancreatic carcinoma

El compromiso primario del páncreas en los linfomas es muy poco frecuente, sin embargo, en los estadios avanzados de los linfomas no Hodgkin la invasión secundaria de la glándula es observada con mayor frecuencia. El objetivo de esta presentación es describir un caso de linfoma de Burkitt en un adulto inmunocompetente que presentó como manifestación relevante colestasis extrahepática secundaria probablemente a infiltración pancreática difusa y tumores cutáneos cuya histología permitió hacer el diagnóstico. Luego de una dosis única de hidrocortisona de 100mg, mejoró la ictericia, disminuyeron las enzimas de colestasis, las lesiones cutáneas y disminuyó el tamaño del páncreas en la ecografía y en la tomografía computada. Existen en la literatura reportes aislados de casos de linfoma tipo Burkitt que se asocian a ictericia obstructiva secundaria y a infiltración pancreática o del hilio hepático, tratándose en su mayoría de casos pediátricos o de individuos afectados por el virus de la inmunodeficiencia humana (VIH). Creemos que el interés de este caso radica en la rápida respuesta a dosis bajas de corticoides de la colestasis, lo que evitó la necesidad de un procedimiento quirúrgico tanto diagnóstico como terapéutico de la obstrucción biliar, como está referido en la literatura, permitiendo instaurar rápidamente el tratamiento quimioterapéutico específico de esta entidad sin maniobras quirúrgicas o endoscópicas.

The primary compromise of the pancreas in lymphomas is uncommon. However, in advanced stages of Non- Hodgkin’s lymphomas (LNH) the secondary invasion of the pancreas is observed more frequently. Jaundice due to extrahepatic cholestasis as a presentation form is extremely rare, with only few cases described in the literature. The aim is to present a case of an obstructive jaundice as an expression of Burkitt’s lymphoma probably due to a diffuse pancreatic infiltration in an adult without immunodeficiency with a rapid response of cholestasis to low dose of hydrocortisone. Skin tumor simultaneously present with jaundice allowed the histologic diagnosis with skin biopsies. After a unique dose of 100 mg hydrocortisone, jaundice improved and cholestatic enzymes decreased, pancreas became smaller and common bile duct diameter became normal at ultrasound and CT scan, also skin tumors turn pale and diminished in size. There are isolated reports of Burkitt’s lymphoma cases with associated obstructive jaundice due to pancreatic infiltration or by compression by lymph nodes of the bile ducts, many of them are pediatric cases or immunodepressed HIV patients. In the case presented, surgical resection of the pancreatic infiltration and biliary drainage, either surgical or endoscopic during the same procedure was not necessary for the histopathologic diagnosis of the illness like is described in the literature. The diagnosis was suspected by the rapid decrease of cholestatic features after a single dose of hydrocortisone and the histology was easy done by a skin biopsy. We think the interest in this case is the quick response to low doses of corticoids, which avoided the necessity of surgical procedure for the diagnosis of the biliary tree obstruction, allowing a quick implementation of the specific chemotherapeutic treatment of the lymphoma without any surgical or endoscopic procedures to heal the jaundice.